Analgesia and Sedation in Patients with COVID-19

Approximately 14 percent of patients with COVID-19 infection experience a severe form of hypoxic
respiratory failure, with 5 percent requiring mechanical ventilation.1 The dyspnea, air hunger, physical
discomfort of being intubated, and need to prevent self-extubation have made sedation of these
patients challenging, with many requiring high doses of multiple medications to achieve comfort.
Moreover, in the subset of patients with low lung compliance and acute respiratory distress syndrome,
use of low tidal volumes, controlled ventilation, and prone positioning require high levels of sedation
and often neuromuscular blockade to permit proper ventilation.2,3

Standard critical care management involves daily interruption of sedation, which reduces the number of
days on the ventilator.4 Attention to sedation is important in the COVID-19 pandemic both for optimal
patient care and because sedative and analgesic medications are in high demand. In March, the demand
for sedatives increased by 91 percent, for analgesics by 79 percent, and for neuromuscular blockers by
105 percent.5

At present, sedation/analgesia regimens are based on standard critical care guidelines, with some
adaptations to the environment. For patients who are not intubated, bolus dosing of hydromorphone or
fentanyl for analgesia and midazolam for sedation/anxiolysis are effective first-line agents. A
dexmedetomidine infusion is another option to provide light to medium sedation while allowing
intermittent patient wakefulness and is effective in patients at risk for or experiencing alcohol
withdrawal.

In intubated patients, a fentanyl infusion is commonly used initially for analgesia, but because of
fentanyl’s lipophilic properties and tachyphylaxis with long-term use, hydromorphone is a good
alternative, with the advantage of being least affected by organ dysfunction. For sedation, propofol is
the usual first choice, with supplementation by intravenous boluses of a benzodiazepine. When heavy
sedation is required, a midazolam or ketamine infusion may be added. For ventilator dyssynchrony
despite adequate sedation, bolus doses of neuromuscular blockers are preferable to continuous
infusions.

To spare intravenous medications to prevent or manage drug shortages, bolus dosing of phenobarbital,
a barbiturate with a long half-life, may be used on a short-term basis. Enteric medications also
frequently are used to spare intravenous supplies, including oxycodone and gabapentin for pain, and
lorazepam or diazepam for sedation and anxiety. Melatonin also has been reported in COVID-19 patients
to spare sedatives and treat agitation.6 The message for sedation and analgesia in the pandemic is to
follow our usual evidence-based critical care guidelines, but be flexible and creative if adjunctive therapy
is needed based on the patient’s response to initial treatment.

References
1. Alhazzani W, Moller MH, Arabi Y, et al. Surviving Sepsis Campaign: Guidelines on the
management of critically ill adults with coronavirus disease 2019 (COVID-19). Int Care Med.
2020. Epub ahead of print 28 March. https://doi.org/10.1007/s00134-020-06022-5
2. Sorbello M, El-Boghdadly K, Di Giacinto I, et al. The Italian coronavirus disease 2019 outbreak:
Recommendations for clinical practice. Anaesthesia. 2020. https://doi:10.1111/anae.15049
3. Matos RI, Chung KK. DoD COVID-19 practice management guide. Clinical management of COVID-
19. Available at: https://jts.amedd.army.mil/. Accessed March 19, 2020.
4. Girard TD, Kress JP, Fuchs BD, et al. Efficacy and safety of a paired sedation and ventilator
weaning protocol for mechanically ventilated patients in intensive care (Awakening and
Breathing Controlled trial): A randomised controlled trial. Lancet. 2008;371;126-134.
5. Vizient. COVID-19 impact on drugs essential for ventilator use.
https://newsroom.vizientinc.com/sites/vha.newshq.businesswire.com/files/doc_library/file/CO
VID-19_impact_on_essential_meds_for_ventilator_use_-_FINAL.pdf
6. Zhang R, Wang X, Ni L, et al. COVID-19: Melatonin as a potential adjuvant treatment. Life
Sciences. Available at: https://doi.org/10.1016/j.lfs.2020.117583. Accessed April 20, 2020.